A molecular diagnostic algorithm for JAK2 V617F investigations in suspected myeloproliferative neoplasms

Catherwood, Mark; McAllister, Roisin; McCallion, Patrick; McGimpsey, Julie; Hindley, Andrew; Feerick, John; Greenfield, Graeme; Kennedy, Paul; Benson, Gary; Arnold, Claire; Merron, Bridgin; McMullin, Mary Frances

doi:10.1007/s11845-019-02100-w

Cited by 3 publications

(4 citation statements)

References 20 publications

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“…As the median duration of clinical follow-up was 10 years all cases were rescreened for the canonical driver mutations by conventional approaches. 5,6 Of interest, six patients were JAK2V617F positive and two patients were CALR positive on repeat screening. (table 2).…”

Section: Molecular Resultsmentioning

confidence: 99%

“…The remaining 10 cases did not have a BM but were considered likely to have a diagnosis of ET because in the past in the real-world setting patients with a persistently elevated platelet count and no other cause have had a diagnosis of ET 4. Patients with suspected TN-ET were included after excluding JAK2 V617F, CALR exon 9 and MPL exon 10 mutations by conventional techniques (allele-specific PCR, DNA fragment analysis and Sanger sequencing, respectively) 5 6…”

Section: Methodsmentioning

confidence: 99%

“…4 Suspected TN-ET patients were included after excluding JAK2V617F, CALR exon 9 and MPL exon 10 mutations by conventional techniques (allelic specific PCR, DNA fragment analysis and Sanger sequencing, respectively). 5,6 Next Generation Sequencing Genomic DNA was extracted from whole peripheral blood and retested for JAK2V617F, CALR exon 9 and MPL exon 10 mutations by conventional techniques. NGS was performed using the Illumina MiSeqTM platform and the Trusight Myeloid gene panel.…”

Section: Data Collectionmentioning

confidence: 99%

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Mutational profiling in suspected triple-negative essential thrombocythaemia using targeted next-generation sequencing in a real-world cohort

et al. 2020

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Essential thrombocythaemia (ET) is driven by somatic mutations involving the JAK2, CALR and MPL genes. Approximately 10% of patients lack driver mutations and are referred as ‘triple-negative’ ET (TN-ET). The diagnosis of TN-ET, however, relies on bone marrow examination that is not always performed in routine practice, and thus in the real-world setting, there are a group of cases with suspected TN-myeloproliferativeneoplasm.In this real-world cohort, patients with suspected TN-ET were initially rescreened for JAK2, CALR and MPL and then targeted next-generation sequencing (NGS) was applied.The 35 patients with suspected TN-ET had a median age at diagnosis of 43 years (range 16–79) and a follow-up of 10 years (range 2–28). The median platelet count was 758×109/L (range 479–2903). Thrombosis prior to and following diagnosis was noted in 20% and 17% of patients. Six patients were JAK2V617F and two patients were CALR positive on repeat screening. NGS results showed that 24 of 27 patients harboured no mutations. Four mutations were noted in three patients.There was no evidence of clonality for the majority of patients with suspected TN-ET with targeted NGS analysis. Detection of driver mutations in those who were previously screened suggests that regular rescreening is required. This study also questions the diagnosis of TN-ET without the existence of a clonal marker.

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Section: Molecular Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Data Collectionmentioning

confidence: 99%

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Mutational profiling in suspected triple-negative essential thrombocythaemia using targeted next-generation sequencing in a real-world cohort

et al. 2020

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“…Many MPN patients harbor somatic mutations in epigenetic regulators as well. For instance, DNA methylation (including TET2, DNMT3A, and IDH1/2) or chromatin structure (contains ASXL1 and EZH2) and accessory mutations in the regulators are proposed to affect MPN specific phenotypes [63,97,98], promote progression, and induce phenotypic switching. In addition to driver mutations, alterations in the function of epigenetic regulators may also act as disease modifiers of MPN [99].…”

Section: Epigenetic Modifiers In Jak2v617f Mpn Phenotypementioning

confidence: 99%

Insights into the Potential Mechanisms of JAK2V617F Somatic Mutation Contributing Distinct Phenotypes in Myeloproliferative Neoplasms

Gou

Zhang

Giraudier

2022

IJMS

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Myeloproliferative neoplasms (MPN) are a group of blood cancers in which the bone marrow (BM) produces an overabundance of erythrocyte, white blood cells, or platelets. Philadelphia chromosome-negative MPN has three subtypes, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The over proliferation of blood cells is often associated with somatic mutations, such as JAK2, CALR, and MPL. JAK2V617F is present in 95% of PV and 50–60% of ET and PMF. Based on current molecular dynamics simulations of full JAK2 and the crystal structure of individual domains, it suggests that JAK2 maintains basal activity through self-inhibition, whereas other domains and linkers directly/indirectly enhance this self-inhibited state. Nevertheless, the JAK2V617F mutation is not the only determinant of MPN phenotype, as many normal individuals carry the JAK2V617F mutation without a disease phenotype. Here we review the major MPN phenotypes, JAK-STAT pathways, and mechanisms of development based on structural biology, while also describing the impact of other contributing factors such as gene mutation allele burden, JAK-STAT-related signaling pathways, epigenetic modifications, immune responses, and lifestyle on different MPN phenotypes. The cross-linking of these elements constitutes a complex network of interactions and generates differences in individual and cellular contexts that determine the phenotypic development of MPN.

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Analysis of Molecular Testing for Suspected Myeloproliferative Neoplasm at a Hybrid Community-Academic Health System

Stone,

Martinez,

Arries

et al. 2025

The Journal of Molecular Diagnostics

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A molecular diagnostic algorithm for JAK2 V617F investigations in suspected myeloproliferative neoplasms

Cited by 3 publications

References 20 publications

Mutational profiling in suspected triple-negative essential thrombocythaemia using targeted next-generation sequencing in a real-world cohort

Mutational profiling in suspected triple-negative essential thrombocythaemia using targeted next-generation sequencing in a real-world cohort

Insights into the Potential Mechanisms of JAK2V617F Somatic Mutation Contributing Distinct Phenotypes in Myeloproliferative Neoplasms

Analysis of Molecular Testing for Suspected Myeloproliferative Neoplasm at a Hybrid Community-Academic Health System

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